干旱区生态环境知识资源中心(Arid): A novel, homozygous mutation in desert hedgehog (DHH) in a 46, XY patient with dysgenetic testes presenting with primary amenorrhoea: a case report

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DOI	10.1186/s13633-018-0056-3
	A novel, homozygous mutation in desert hedgehog (DHH) in a 46, XY patient with dysgenetic testes presenting with primary amenorrhoea: a case report
	Rothacker, Karen M.; Ayers, Katie L.; Tang, Dave; Joshi, Kiranjit; van den Bergen, Jocelyn A.; Robevska, Gorjana; Samnakay, Naeem; Nagarajan, Lakshmi; Francis, Kate; Sinclair, Andrew H.; Choong, Catherine S.
通讯作者	Rothacker, KM
来源期刊	INTERNATIONAL JOURNAL OF PEDIATRIC ENDOCRINOLOGY
ISSN	1687-9848
EISSN	1687-9856
出版年	2018
英文摘要	Background: Desert hedgehog (DHH) mutations have been described in only a limited number of individuals with 46, XY disorders of sex development (DSD) presenting as either partial or complete gonadal dysgenesis. Gonadal tumours and peripheral neuropathy have been associated with DHH mutations. Herein we report a novel, homozygous mutation of DHH identified through a targeted, massively parallel sequencing (MPS) DSD panel, in a patient presenting with partial gonadal dysgenesis. This novel mutation is two amino acids away from a previously described mutation in a patient who presented with complete gonadal dysgenesis. Adding to the complexity of work-up, our patient also expressed gender identity concern. Case presentation: A 14-year-old, phenotypic female presented with primary amenorrhoea and absent secondary sex characteristics. Investigations revealed elevated gonadotrophins with low oestradiol, testosterone of 0.6 nmol/L and a 46, XY karyotype. Mullerian structures were not seen on pelvic ultrasound or laparoscopically and gonadal biopsies demonstrated dysgenetic testes without neoplasia (partial gonadal dysgenesis). The patient expressed gender identity confusion upon initial notification of investigation findings. Formal psychiatric evaluation excluded gender dysphoria. Genetic analysis was performed using a targeted, MPS DSD panel of 64 diagnostic and 927 research candidate genes. This identified a novel, homozygous mutation in exon 2 of DHH (DHH: NM_021044: exon2: c.G491C: p.R164P). With this finding our patient was screened for the possibility of peripheral neuropathy which was not evident clinically nor on investigation. She was commenced on oestrogen for pubertal induction. Conclusion: The evaluation of patients with DSD is associated with considerable psychological distress. Targeted MPS enables an affordable and efficient method for diagnosis of 46, XY DSD cases. Identifying a genetic diagnosis may inform clinical management and in this case directed screening for peripheral neuropathy. In addition to the structural location of the mutation other interacting factors may influence phenotypic expression in homozygous DHH mutations.
英文关键词	Disorder of sex development Desert hedgehog DHH Gonadal dysgenesis Massively parallel sequencing
类型	Article
语种	英语
开放获取类型	DOAJ Gold, Green Published
收录类别	ESCI
WOS记录号	WOS:000426507200001
WOS关键词	SEX DEVELOPMENT INSIGHTS ; GONADAL-DYSGENESIS ; MINIFASCICLE FORMATION ; DISORDERS ; GENE ; NEUROPATHY ; VARIANT
WOS类目	Endocrinology & Metabolism
WOS研究方向	Endocrinology & Metabolism
Scopus学科分类	Princess Margaret Hosp, Dept Endocrinol & Diabet, GPO Box D 184, Perth, WA, Australia.
来源机构	University of Western Australia
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/332718
作者单位	[Rothacker, Karen M.; Joshi, Kiranjit; Choong, Catherine S.] Princess Margaret Hosp, Dept Endocrinol & Diabet, Subiaco, WA, Australia; [Ayers, Katie L.; van den Bergen, Jocelyn A.; Robevska, Gorjana; Sinclair, Andrew H.] Murdoch Childrens Res Inst, Melbourne, Vic, Australia; [Ayers, Katie L.; Sinclair, Andrew H.] Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia; [Tang, Dave] Telethon Kids Inst, Subiaco, WA, Australia; [Samnakay, Naeem] Princess Margaret Hosp, Dept Paediat Surg, Subiaco, WA, Australia; [Samnakay, Naeem] Univ Western Australia, Sch Surg, Crawley, WA, Australia; [Nagarajan, Lakshmi] Princess Margaret Hosp, Dept Neurol, Subiaco, WA, Australia; [Nagarajan, Lakshmi; Choong, Catherine S.] Univ Western Australia, Sch Paediat & Child Hlth, Crawley, WA, Australia; [Francis, Kate] Queen Elizabeth II Med Ctr, PathWest Lab Med, Dept Anat Pathol, Nedlands, WA, Australia; [Sinclair, Andrew H.] Victorian Clin Genet Serv, Melbourne, Vic, Australia; [Rothacker, Karen M.] Princess Margaret Hosp, Dept...
推荐引用方式 GB/T 7714	Rothacker, Karen M.,Ayers, Katie L.,Tang, Dave,et al. A novel, homozygous mutation in desert hedgehog (DHH) in a 46, XY patient with dysgenetic testes presenting with primary amenorrhoea: a case report[J]. University of Western Australia,2018.
APA	Rothacker, Karen M..,Ayers, Katie L..,Tang, Dave.,Joshi, Kiranjit.,van den Bergen, Jocelyn A..,...&Choong, Catherine S..(2018).A novel, homozygous mutation in desert hedgehog (DHH) in a 46, XY patient with dysgenetic testes presenting with primary amenorrhoea: a case report.INTERNATIONAL JOURNAL OF PEDIATRIC ENDOCRINOLOGY.
MLA	Rothacker, Karen M.,et al."A novel, homozygous mutation in desert hedgehog (DHH) in a 46, XY patient with dysgenetic testes presenting with primary amenorrhoea: a case report".INTERNATIONAL JOURNAL OF PEDIATRIC ENDOCRINOLOGY (2018).